Structured treatment interruption in HIV-infected patients failing on multidrug therapy: is there a future for this strategy?

Abstract

Among factors that might limit the benefits of highly active antiretroviral therapy (HAART) other than suboptimal medication adherence and drug toxicities most concern centred on the development of resistant viral variants which can compromise the virological response rate of treatment regimens. Large surveys of HAART-experienced populations have shown that the probability of developing a multiclass drug resistance is approximately 20–42% after several years of treatment. Therefore interest has grown in developing new strategies for patients with few or no therapeutic options because of the presence of multidrug-resistant viral strains. One of the critical points under discussion is whether complete viral suppression represents the preferred endpoint of clinical strategy in this late phase of the natural history of treatment. Several observations suggest that drug-resistant HIV-1 has differing degrees of decreased replicative capacity compared with wild-type virus. Consequently discontinuation of antiretroviral therapy in patients with multidrug-resistant virus may rapidly cause overgrowth by wild-type virus with a hypothetical decline of resistance and reversion of genotypic mutations. However maintaining a failed regimen to which HIV is resistant may still keep viral replicative capacity low and so the likelihood of immunological deterioration and clinic progression could be reduced. (excerpt)